DepressionNCT03276793
Brain Connectivity in Depression
A study testing MRI scan and Behavioral testing in people with Depression, run by Brigham and Women's Hospital at 4 sites in United States.
Trial summary
This study originally included 140 subjects with medication-refractory depression undergoing 10 Hz transcranial magnetic stimulation (10Hz-TMS) to the left dorsal lateral prefrontal cortex (DLPFC), with the goal of having 60 completers with good quality data. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression
- What is being tested?
- MRI scan and Behavioral testing
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- 4 sitesUnited States
- Study dates
- 3 Apr 2018to 31 Oct 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female
- Aged 18 or older
- Have previously received or will once daily TMS treatment to the left dorsolateral prefrontal cortex at the Center for Brain Circuit Therapeutics at Brigham and Women's Hospital, or at Massachusetts General Hospital for treatment of medication resistant depression
Who cannot join
- Presence of a significant neurologic disorder (i.e. Parkinson's Disease, stroke, Alzheimer's Disease, tumor, multiple sclerosis, epilepsy) or other significant active medical problems which may impact treatment or safety. Of note, many of these are also contraindications to receiving TMS and these patients would not be enrolled in the clinical treatment program. Because these diagnoses, their significance, and the extent to which they are an active issue can be subjective, each of these exclusions (1-3) will be reviewed by the PI or study physician
- Lack of response to an adequate trial of electroconvulsive therapy (ECT) or any ECT in the preceding 3 months
- Prior adequate trial of TMS treatment in the last 12 months
- Positive MRI screen that would preclude the subject from undergoing magnetic resonance imaging. These include, but are not limited to any of the following:
- Known metal in the head (such as a surgical aneurysm clip), or a history of prior neurosurgical procedures
- Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic means such as: cochlear implants, pacemakers, medication pumps, vagal stimulators, deep brain stimulators, neurostimulators, biostimulators, or ventriculo-peritoneal shunts
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- Subjects who have or might have bullet fragments or other metal fragments (veterans or workers exposed to metal in their work environment)
- Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic eyeliner)
- Subjects expressing significant anxiety or claustrophobia about being in the magnet.
- Subjects that cannot adhere to the experimental protocol for any reason.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Emma Jones, BS contact
United States4 sites, 2 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Michael D Fox, MD, PhD, 617-732-7432, bwh_fdctrial@mgb.org
Michael D Fox, MD, PhD
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02129
Tracy A Barbour, MD, 617-726-5340, TBARBOUR@PARTNERS.ORG
Luke Janak, BS, Ljanak@mgh.harvard.edu
- Completed
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
- Active, not recruiting
Butler Hospital
Providence, Rhode Island, 02906
About this study
Official title: Using Human Brain Connectivity to Identify the Causal Neuroanatomical Substrate of Depression Symptoms
This study originally included 140 subjects with medication-refractory depression undergoing 10 Hz transcranial magnetic stimulation (10Hz-TMS) to the left dorsal lateral prefrontal cortex (DLPFC), with the goal of having 60 completers with good quality data. Subjects were recruited from the TMS clinics at Beth Israel Deaconess Medical Center, Brigham \& Women's Hospital, and Butler Hospital. Subjects underwent an hour-long MRI scanning session, an optional DNA-sample collection, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), War Game (Gambling) task, and Associative Learning with Reversal task. Subjects' scores on the Quick Inventory of Depressive Symptomatology (QIDS) and Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data was utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement. This was the only study group until August 30, 2022, and the primary outcome was analyzed for the 10Hz-TMS group.
Due to changes in clinical standard of care from 10Hz-TMS to a newer version of TMS termed intermittent theta burst (iTBS), in September 2022 a second group was added to include patients receiving this new form of TMS. This second group included another 100 patients with medication-refractory depression undergoing iTBS to the left dorsal lateral prefrontal cortex (DLPFC), with the intent to have 80 completers. Massachusetts General Hospital was added as a data collection site in lieu of Butler Hospital. Subjects will undergo an hour-long MRI scanning session, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery will included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), Penn Emotion Recognition Test, the Suicide/Death Implicit Association Test, and Associative Learning with Reversal task. Subjects' scores on the Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data will be utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement.
Due to a higher dropout rate than anticipated, in March of 2025 an amendment was added to include an additional 20 subjects in the second group's enrollment goal to increase the likelihood of achieving 80 completers.
Read the detailed description
This study was originally approved by the Beth Israel Deaconess Medical Center (BIDMC) Institutional Review Board (IRB) with Butler Hospital as a relying site. The study was transferred to the Mass General Brigham (MGB) IRB in 2020 when Dr. Fox (lead PI) moved to Brigham and Women's Hospital (BWH). Butler Hospital continued to enroll subjects, relying on the MGB IRB for regulatory oversight, while BIDMC stopped enrolling subjects. A Data Usage Agreement was established between BIDMC and BWH, and all previously collected Data was de-identified and sent to BWH. The protocol at BIDMC will remain active but not enrolling until all the de-identified data has been sent to BWH.
In Sept 2022, with the launch of the second iTBS group, Massachusetts General Hospital replaced Butler Hospital as the secondary enrollment site, while enrollment continued at Brigham and Women's Hospital.
- Conditions
- Depression
- Being tested
- MRI scan, Behavioral testing
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI scanOther
Patients will undergo an MRI scan
Behavioral testingBehavioural
Patients will complete a series of cognitive tasks
| Study group | Role | What they receive |
|---|---|---|
| MRI and behavioral assessment for patients receiving TMS | Experimental | Subjects will undergo an hour-long MRI scanning session, a marking for the site of planned clinical TMS stimulation and a behavioral testing battery before and after their TMS treatment course. Receives: Other: MRI scan; Behavioral: Behavioral testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prediction of repetitive Transcranial Magnetic Stimulation (rTMS) clinical response
Connectivity between each patient's stimulation site and the subgenual cingulate will be used to predict clinical response to rTMS in the first group (data collected starting in 2017).
Measured: 1 year after study completion
Prediction of intermittent theta burst stimulation (iTBS) clinical response
Normative connectivity of each patient's stimulation site to a previously-published "depression network" (Siddiqi et al., Nat Hum Behav 2021) will be used to predict clinical response to iTBS in the second group added in September 2022.
Measured: 1 year after study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study start3 Apr 2018
- Primary completion30 Sep 2027 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 260 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Butler Hospital, Massachusetts General Hospital, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Michael D. Fox, M.D.,Ph.D., Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03276793
- Sponsor's protocol ID
- 2021P000335
- Other IDs
- R01MH113929
- Status last verified
- Apr 2025
- First submitted
- 5 Sep 2017
- Last updated
- 21 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Khosravani S, Palm ST, Drew W, Frandsen SB, Lin C, Tirrell E, Hindley L, Schineller M, Garimella A, Chiulli N, Lawson D, Jones E, Press DZ, Stern AP, Brown JC, Barbour TA, Taylor JJ, Carpenter LL, Siddiqi SH, Fox MD. Predictive value of subgenual cingulate normative connectivity to TMS treatment site for antidepressant response in routine clinical practice: a prospective, multisite cohort study. Mol Psychiatry. 2026 Feb;31(2):689-700. doi: 10.1038/s41380-025-03153-3. Epub 2025 Aug 22.
PubMed 40847007
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Human Brain Connectivity to Identify the Causal Neuroanatomical Substrate of Depression Symptoms
- ClinicalTrials.gov ID
- NCT03276793
- Acronym / sponsor ID
- 2021P000335
- Conditions
- Depression
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 260 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Butler Hospital, Massachusetts General Hospital, National Institute of Mental Health (NIMH)
- Study start
- 3 Apr 2018 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 8 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study originally included 140 subjects with medication-refractory depression undergoing 10 Hz transcranial magnetic stimulation (10Hz-TMS) to the left dorsal lateral prefrontal cortex (DLPFC), with the goal of having 60 completers with good quality data. Subjects were recruited from the TMS clinics at Beth Israel Deaconess Medical Center, Brigham \& Women's Hospital, and Butler Hospital. Subjects underwent an hour-long MRI scanning session, an optional DNA-sample collection, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), War Game (Gambling) task, and Associative Learning with Reversal task. Subjects' scores on the Quick Inventory of Depressive Symptomatology (QIDS) and Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data was utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement. This was the only study group until August 30, 2022, and the primary outcome was analyzed for the 10Hz-TMS group.
Due to changes in clinical standard of care from 10Hz-TMS to a newer version of TMS termed intermittent theta burst (iTBS), in September 2022 a second group was added to include patients receiving this new form of TMS. This second group included another 100 patients with medication-refractory depression undergoing iTBS to the left dorsal lateral prefrontal cortex (DLPFC), with the intent to have 80 completers. Massachusetts General Hospital was added as a data collection site in lieu of Butler Hospital. Subjects will undergo an hour-long MRI scanning session, up to three 20 minute neuronavigation sessions for marking the site of TMS stimulation, questionnaires, and a behavioral testing battery before and after their TMS treatment course. The task battery will included the Emotion Conflict Resolution (ECR) task, Multi-Source Interference Task (MSIT), Penn Emotion Recognition Test, the Suicide/Death Implicit Association Test, and Associative Learning with Reversal task. Subjects' scores on the Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data will be utilized to identify brain regions whose connectivity to the stimulation site co-varies with the aforementioned measures of symptom improvement.
Due to a higher dropout rate than anticipated, in March of 2025 an amendment was added to include an additional 20 subjects in the second group's enrollment goal to increase the likelihood of achieving 80 completers.
Detailed description
This study was originally approved by the Beth Israel Deaconess Medical Center (BIDMC) Institutional Review Board (IRB) with Butler Hospital as a relying site. The study was transferred to the Mass General Brigham (MGB) IRB in 2020 when Dr. Fox (lead PI) moved to Brigham and Women's Hospital (BWH). Butler Hospital continued to enroll subjects, relying on the MGB IRB for regulatory oversight, while BIDMC stopped enrolling subjects. A Data Usage Agreement was established between BIDMC and BWH, and all previously collected Data was de-identified and sent to BWH. The protocol at BIDMC will remain active but not enrolling until all the de-identified data has been sent to BWH.
In Sept 2022, with the launch of the second iTBS group, Massachusetts General Hospital replaced Butler Hospital as the secondary enrollment site, while enrollment continued at Brigham and Women's Hospital.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MRI and behavioral assessment for patients receiving TMS | Experimental | Other: MRI scan, Behavioral: Behavioral testingSubjects will undergo an hour-long MRI scanning session, a marking for the site of planned clinical TMS stimulation and a behavioral testing battery before and after their TMS treatment course. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female
- Aged 18 or older
- Have previously received or will once daily TMS treatment to the left dorsolateral prefrontal cortex at the Center for Brain Circuit Therapeutics at Brigham and Women's Hospital, or at Massachusetts General Hospital for treatment of medication resistant depression
Key exclusion criteria (10 listed)
- Presence of a significant neurologic disorder (i.e. Parkinson's Disease, stroke, Alzheimer's Disease, tumor, multiple sclerosis, epilepsy) or other significant active medical problems which may impact treatment or safety. Of note, many of these are also contraindications to receiving TMS and these patients would not be enrolled in the clinical treatment program. Because these diagnoses, their significance, and the extent to which they are an active issue can be subjective, each of these exclusions (1-3) will be reviewed by the PI or study physician
- Lack of response to an adequate trial of electroconvulsive therapy (ECT) or any ECT in the preceding 3 months
- Prior adequate trial of TMS treatment in the last 12 months
- Positive MRI screen that would preclude the subject from undergoing magnetic resonance imaging. These include, but are not limited to any of the following:
- Subjects that cannot adhere to the experimental protocol for any reason.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI scanPatients will undergo an MRI scan | Other | MRI and behavioral assessment for patients receiving TMS |
| Behavioral testingPatients will complete a series of cognitive tasks | Behavioural | MRI and behavioral assessment for patients receiving TMS |
Primary outcome
Prediction of repetitive Transcranial Magnetic Stimulation (rTMS) clinical response
Time frame: 1 year after study completion
Connectivity between each patient's stimulation site and the subgenual cingulate will be used to predict clinical response to rTMS in the first group (data collected starting in 2017).
Prediction of intermittent theta burst stimulation (iTBS) clinical response
Time frame: 1 year after study completion
Normative connectivity of each patient's stimulation site to a previously-published "depression network" (Siddiqi et al., Nat Hum Behav 2021) will be used to predict clinical response to iTBS in the second group added in September 2022.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2025.
- Derived from this study: PubMed 40847007Khosravani S, Palm ST, Drew W, Frandsen SB, Lin C, Tirrell E, Hindley L, Schineller M, Garimella A, Chiulli N, Lawson D, Jones E, Press DZ, Stern AP, Brown JC, Barbour TA, Taylor JJ, Carpenter LL, Siddiqi SH, Fox MD. Predictive value of subgenual cingulate normative connectivity to TMS treatment site for antidepressant response in routine clinical practice: a prospective, multisite cohort study. Mol Psychiatry. 2026 Feb;31(2):689-700. doi: 10.1038/s41380-025-03153-3. Epub 2025 Aug 22.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Emma Jones, BS contact
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MRI scan and Behavioral testing in people with Depression, run by Brigham and Women's Hospital at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Lawson, BA (617-732-6658, bwh_fdctrial@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prediction of repetitive Transcranial Magnetic Stimulation (rTMS) clinical response (time frame: 1 year after study completion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03276793, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2025.